Studies on the molecular mechanisms of Meclizine-induced cell cycle arrest and apoptosis in human colon adenocarcinoma cells
| Autor: | Jiunn-Chang Lin, 林俊昌 |
|---|---|
| Rok vydání: | 2003 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 91 Meclizine, a kind of histamine H1 antagonist, has been used in the treatment of motion sickness and vertigo. In studying the interaction of drugs and cancer cell lines, we have found that meclizine dose-dependently induced apoptosis in COLO 205 cells. By DNA ladder assay, we demonstrated that DNA ladder appeared with meclizine treatment in COLO 205 cells if dosage larger than 50 μM. Besides, we observed that cell numbers decreased dose-dependently after treatment with meclizine in COLO 205 cells. By flow cytometry, we noticed that the percentage of COLO 205 cells in G0/G1 phase increased dose-dependently. We analyzed the change of associated protein by Western blot. About cell cycle arrest, p53 and p21 were upregulated after treatment with meclizine and resulted in decreasing CDK2 and CDK4 kinase activity. About apoptosis, meclizine induces upregulation of p53, downregulation of Bcl-2, release of cytochrome C into cytosol from mitochondria, translocation of AIF to the nucleus from mitochondria, and activation of caspase 3, caspase 8, and caspase 9. According to these data and concepts from references, we propose a flowchart to explain the possible mechanism of meclizine-induced apoptosis and cell cycle arrest in COLO 205 cell. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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